RESUMEN
PURPOSE: The purpose of this study was to resolve the issue of whether various generations of CR Bard peripheral vascular access ports and catheters are prone to retain PET radiopharmaceuticals. The study evaluates the residual radioactivity remaining following injection for two PET radiopharmaceuticals currently used extensively in the clinic, FDG and Na18 F. METHODS: FDG was purchased from a local cyclotron facility and Na18 F was prepared in-house. Three generations of currently marketed vascular access ports were tested. A total of five (n = 5) of each model was tested. Radiopharmaceutical of 2-3 mCi of each was injected into each port and flushed with 10, 30, 60, and 120 ml of saline. MicroPET scans were performed after each flush to detect the residual radioactivity on each port. A dose calibrator was used to detect the retention of radioactivity after each flush. RESULTS: Radioactivity retention for all vascular port models measured by microPET imaging was similar for both FDG and Na18 F, with less than 1% residual activity following a 10 ml saline flush. Based on the microPET images, all the subsequent flushes of 30, 60, and 120 ml were also considered. Dose calibrator activity measurements validated microPET measurements as negligible for all the ports, even with the first 10 ml flush. CONCLUSIONS: MicroPET imaging was more sensitive than the dose calibrator in determining the radioactivity retention of the vascular access ports from CR Bard. These ports may be used for the injection of FDG and Na18 F to track glucose metabolism and bone uptake with PET imaging. It is recommended to apply at least a 10 ml flush after radiopharmaceutical administration, to reduce residual activity to baseline levels.
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Fluorodesoxiglucosa F18/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía de Emisión de Positrones/instrumentación , Tomografía de Emisión de Positrones/métodos , Radiofármacos/metabolismo , Dispositivos de Acceso Vascular/normas , Humanos , Ensayo de MaterialesRESUMEN
The process for validating dose-volume histogram data in brachytherapy software is presented as a supplement to a previously published article. Included is the DVH accuracy evaluation of the Best NOMOS treatment planning system called "Best TPS VolumePlan." As done previously in other software, a rectangular cuboid was contoured in the treatment planning system. A single radioactive 125I source was positioned coplanar and concentric with one end. Calculations were performed to estimate dose deposition in partial volumes of the cuboid structure, using the brachytherapy dosimetry formalism defined in AAPM Task Group 43. Hand-calculated, dose-volume results were compared to TPS-generated, point-source-approximated dose-volume histogram data to establish acceptance. The required QA for commissioning was satisfied for the DVH as conducted previously for other software, using the criterion that the DVH %VolTPS "actual variance" calculations should differ by no more than 5% at any specific radial distance with respect to %VolTG-43, and the "average variance" DVH %VolTPS calculations should differ by no more than 2% over all radial distances with respect to %VolTG-43. The average disagreement observed between hand calculations and treatment planning system DVH was less than 0.5% on average for this treatment planning system and less than 1.1% maximally for 1 ≤ r ≤ 5 cm.
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Braquiterapia/métodos , Radioisótopos de Yodo/química , Modelos Estadísticos , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Humanos , Método de Montecarlo , Control de Calidad , Dosificación Radioterapéutica , Programas InformáticosRESUMEN
OBJECTIVE: This testing was conducted to determine if exposure from a particle accelerator used to treat cancer patients would alter the performance of the EndoStim® neurostimulator when programmed either passively or actively and while being irradiated. METHODS: A total of 12 EndoStim Lower Esophageal Sphincter (LES) Stimulation System implantable neurostimulators were investigated in this research. Included were six each of the EndoStim I and EndoStim II. Half were used for passive testing, with the remaining half for active testing. Bremsstrahlung x-rays were delivered having a nominal energy of 18 MV at a rate of 6 Gy/min. A total dose of 80 Gy was achieved in testing minimally. RESULTS: Monitoring of stimulation frequency, amplitude, pulse width, stimulation time, and voltage was conducted using software developed by EndoStim along with an oscilloscope. No observed changes to the intended stimulation were noted and all scheduled parameter magnitudes were achieved with device operation. All functional parameter changes were within ±10% from baseline. CONCLUSIONS: EndoStim I and EndoStim II implant pulse generators appear to be immune to x-ray radiation from the particle accelerator at energies up to 18 MV, at dose rates of up to 6 Gy/min, and up to cumulative doses of minimally 80 Gy. As there were no observable effects on neurostimulation requirements, the EndoStim LES Stimulation System implantable neurostimulators are capable of withstanding direct radiation. The recommendations of the manufacturer should be followed further regarding the labeling requirements for insured safety to patients.
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Terapia por Estimulación Eléctrica/instrumentación , Terapia por Estimulación Eléctrica/métodos , Esfínter Esofágico Inferior/efectos de la radiación , Neuroestimuladores Implantables , Aceleradores de Partículas , Radiación , Relación Dosis-Respuesta en la Radiación , Esfínter Esofágico Inferior/fisiología , Humanos , Aceleradores de Partículas/instrumentaciónRESUMEN
The first quality assurance process for validating dose-volume histogram data involving brachytherapy procedures in radiation therapy is presented. The process is demonstrated using both low dose-rate and high dose-rate radionuclide sources. A rectangular cuboid was contoured in five commercially available brachytherapy treatment planning systems. A single radioactive source commissioned for QA testing was positioned coplanar and concentric with one end. Using the brachytherapy dosimetry formalism defined in the AAPM Task Group 43 report series, calculations were performed to estimate dose deposition in partial volumes of the cuboid structure. The point-source approximation was used for a 125I source and the line-source approximation was used for a 192Ir source in simulated permanent and temporary implants, respectively. Hand-calculated, dose-volume results were compared to TPS-generated, dose-volume histogram (DVH) data to ascertain acceptance. The average disagreement observed between hand calculations and the treatment planning system DVH was less than 1% for the five treatment planning systems and less than 5% for 1 cm ≤ r ≤ 5 cm. A reproducible method for verifying the accuracy of volumetric statistics from a radiation therapy TPS can be employed. The process satisfies QA requirements for TPS commissioning, upgrading, and annual testing. We suggest that investigations be performed if the DVH %Vol(TPS) "actual variance" calculations differ by more than 5% at any specific radial distance with respect to %Vol(TG-43), or if the "average variance" DVH %Vol(TPS) calculations differ by more than 2% over all radial distances with respect to %Vol(TG-43).
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Braquiterapia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Radioisótopos de Yodo/química , Radioisótopos de Iridio/química , Modelos Estadísticos , Método de Montecarlo , Control de Calidad , Radioisótopos/uso terapéutico , Radiometría/métodos , Dosificación Radioterapéutica , Reproducibilidad de los ResultadosRESUMEN
The aim of this study was to assess the performance of a gantry-mounted detector system and a couch set detector system using a systematic multileaf collimator positional error manually introduced for volumetric-modulated arc therapy. Four head and neck and esophagus VMAT plans were evaluated by measurement using an electronic portal imaging device and an ion chamber array. Each plan was copied and duplicated with a 1 mm systematic MLC positional error in the left leaf bank. Direct comparison of measurements for plans with and without the error permitted observational characteristics for quality assurance performance between detectors. A total of 48 different plans were evaluated for this testing. The mean percentage planar dose differences required to satisfy a 95% match between plans with and without the MLCPE were 5.2% ± 0.5% for the chamber array with gantry motion, 8.12% ± 1.04% for the chamber array with a static gantry at 0°, and 10.9%± 1.4% for the EPID with gantry motion. It was observed that the EPID was less accurate due to overresponse of the MLCPE in the left leaf bank. The EPID always images bank-A on the ipsilateral side of the detector, whereas for a chamber array or for a patient, that bank changes as it crosses the -90° or +90° position. A couch set detector system can reproduce the TPS calculated values most consistently. We recommend it as the most reliable patient specific QA system for MLC position error testing. This research is highlighted by the finding of up to 12.7% dose variation for H/N and esophagus cases for VMAT delivery, where the mere source of error was the stated clinically acceptability of 1 mm MLC position deviation of TG-142.
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Lechos , Análisis de Falla de Equipo/instrumentación , Posicionamiento del Paciente/instrumentación , Radiometría/instrumentación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/instrumentación , Diseño de Equipo , Radiometría/métodos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECT: Where no society-based or manufacturer guidance on radiation limits to neuromodulation devices is available, this research provides the groundwork for neurosurgeons and radiation oncologists who rely on the computerized treatment plan clinically for cancer patients. The focus of the article is to characterize radiation parameters of attenuation and scatter when an incident therapeutic x-ray beam is directed upon them. At the time of this writing, manufacturers of Neuromodulation products do not recommend direct exposure of the device in the beam nor provide guidance for the maximum dose for these devices. METHODS: Ten neuromodulation models were chosen to represent the finite class of devices marketed by Medtronic before 2011. CT simulations permitted computer treatment modeling for dose distribution analysis as used routinely in radiation oncology for patients. Phantom case results were directly compared to actual clinical patient cases. Radiation detection measurements were then correlated to computational results. Where the x-ray beam passes through the device and is attenuated, dose reduction was identified with Varian Eclipse computer modeling for these posterior locations. RESULTS: Although the computer algorithm did not identify physical processes of side-scatter and back-scatter, these phenomena were proven by radiation measurement to occur. In general, the computer results underestimated the level of change seen by measurement. CONCLUSIONS: For these implantable neurostimulators, the spread in dose changes were found to be -6.2% to -12.5% by attenuation, +1.7% to +3.8% by side-scatter, and +1.1% to +3.1% by back-scatter at 6 MV. At 18 MV, these findings were observed to be -1.4% to -7.0% by attenuation, +1.8% to 5.7% by side-scatter, and 0.8% to 2.7% by back-scatter. No pattern for the behavior of these phenomena was deduced to be a direct consequence of device size.
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Neuroestimuladores Implantables , Modelos Teóricos , Dosificación Radioterapéutica/normas , Planificación de la Radioterapia Asistida por Computador/normas , Simulación por Computador , Humanos , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos XRESUMEN
This study assesses the dose level from skyshine produced by a 6 MeV medical accelerator. The analysis of data collected on skyshine yields professional guidance for future investigators as they attempt to quantify and qualify radiation protection concerns in shielding therapy vaults. Survey measurements using various field sizes and at varying distances from a primary barrier have enabled us to identify unique skyshine behavior in comparison to other energies already seen in literature. In order to correctly quantify such measurements outside a shielded barrier, one must take into consideration the fact that a skyshine maximum may not be observed at the same distance for all field sizes. A physical attribute of the skyshine scatter component was shown to increase to a maximum value at 4.6 m from the barrier for the largest field size used. We recommend that the largest field sizes be used in the field for the determination of skyshine effect and that the peak value be further analyzed specifically when considering shielding designs.
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Aceleradores de Partículas/instrumentación , Monitoreo de Radiación/métodos , Protección Radiológica/métodos , Radioterapia/instrumentación , Gráficos por Computador , Humanos , Dosis de Radiación , Dispersión de RadiaciónRESUMEN
We detail, derive and correct the technical use of the solid angle variable identified in formal guidance that relates skyshine calculations to dose-equivalent rate. We further recommend it for use with all National Council on Radiation Protection and Measurements (NCRP), Institute of Physics and Engineering in Medicine (IPEM) and similar reports documented. In general, for beams of identical width which have different resulting areas, within ± 1.0 % maximum deviation the analytical pyramidal solution is 1.27 times greater than a misapplied analytical conical solution through all field sizes up to 40 × 40 cm². Therefore, we recommend determining the exact results with the analytical pyramidal solution for square beams and the analytical conical solution for circular beams.
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Monitoreo de Radiación , Protección Radiológica , Radiometría , Simulación por Computador , Humanos , Dosificación RadioterapéuticaRESUMEN
Recent improvements to the functionality and stability of implantable pacemakers and cardioverter-defibrillators involve changes that include efficient battery power consumption and radiation hardened electrical circuits. Manufacturers have also pursued MRI-compatibility for these devices. While such newer models of pacemakers and cardioverter-defibrillators are similar in construction to previously marketed devices - even for the recent MRI-compatible designs currently in clinical trials - there is increased interest now with regard to radiation therapy dose effects when a device is near or directly in the field of radiation. Specifically, the limitation on dose to the device from therapeutic radiation beams is being investigated for a possible elevation in limiting dose above 200 cGy. We present here the first-ever study that evaluates dosimetric effects from implantable pacemakers and implantable cardioverter-defibrillators in high energy X-ray beams from a medical accelerator. Treatment plan simulations were analyzed for four different pacemakers and five different implantable cardioverter-defibrillators and intercompared with direct measurements from a miniature ionization chamber in water. All defibrillators exhibited the same results and all pacemakers were seen to display the same consequences, within only a +/- 1.8% deviation for all X-ray energies studied. Attenuation, backscatter, and lateral scatter were determined to be -13.4%, 2.1% and 1.5% at 6 MV, and -6.1%, 3.1% and 5.1% at 18 MV for the defibrillator group. For the pacemaker group, this research showed results of -15.9%, 2.8% and 2.5% at 6 MV, and -9.4%, 3.4% and 5.7% at 18 MV, respectively. Limited results were discovered from scattering processes through computer modeling. Strong verification from measurements was concluded with respect to simulating attenuation characteristics. For IP and ICD leads, measured dose changes were less than 4%, existing as attenuation processes only, and invariant with regard to X-ray energy.
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Desfibriladores Implantables , Marcapaso Artificial , Radioterapia/efectos adversos , Simulación por Computador , Humanos , Modelos Biológicos , Aceleradores de Partículas , Radiometría , Radioterapia/métodos , Radioterapia/normas , Dosificación Radioterapéutica , Radioterapia de Alta Energía , Rayos XRESUMEN
Vascular access ports are used widely in the administering of drugs for radiation oncology patients. Their dosimetric effect on radiation therapy delivery in photon beams has not been rigorously established. In this work the effects on external beam fields when any of a variety of vascular access ports is included in the path of a high energy beam are studied. This medical physics study specifically identifies side-scatter and back-scatter consequences as well as attenuation effects. The study was divided into two parts: Firstly, a total of 18 ports underwent extended HU range CT scanning followed by 3-D computer treatment planning, where independent homogeneity and heterogeneity plans were created for photon beams of energy 6 MV and 18 MV using a Pencil Beam Convolution (PBC) algorithm. Dose points were analyzed at locations all around each device. A total of 1,440 points were reviewed in this section of the study. Secondly, a mock-up of the largest vascular access port was created in the treatment planning workspace for further investigation with alternative treatment planning algorithms. Plans were generated identically to the above and compared to the results of dose computation between the Pencil Beam Convolution algorithm, the Analytical Anisotropic Algorithm (AAA), and the EGSnrc Monte Carlo algorithm with user code DOSRZnrc (MC). A total of 300 points were reviewed in this part of the study. It was conclusive that ports with more bulky construction and those with partial metal composition create the largest changes. Similar effects are seen for similar port configurations. Considerable differences between the PBC and AAA in comparison to MC are noted and discussed. By thorough examination of planning system results, the presented vascular access ports may now be ranked according to the greatest amount of change exhibited within a treatment planning system. Effects of backscatter, lateral scatter and attenuation are up to 5.0%, 3.4% and 16.8% for 6 MV and 7.0%, 7.7% and 7.2% for 18 MV respectively.
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Fotones , Catéteres de Permanencia , Relación Dosis-Respuesta en la Radiación , Humanos , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Managing radiotherapy patients with implanted cardiac devices (implantable cardiac pacemakers and implantable cardioverter-defibrillators) has been a great practical and procedural challenge in radiation oncology practice. Since the publication of the AAPM TG-34 in 1994, large bodies of literature and case reports have been published about different kinds of radiation effects on modern technology implantable cardiac devices and patient management before, during, and after radiotherapy. This task group report provides the framework that analyzes the potential failure modes of these devices and lays out the methodology for patient management in a comprehensive and concise way, in every step of the entire radiotherapy process.
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Desfibriladores Implantables , Marcapaso Artificial , Radioterapia/métodos , Informe de Investigación , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
BACKGROUND: With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. AIMS: This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. MATERIALS & METHODS: We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. RESULTS: We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. DISCUSSION: Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. CONCLUSION: Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.
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Dosis de Radiación , Radioterapia Guiada por Imagen/métodos , Informe de Investigación , Tomografía Computarizada de Haz Cónico , Humanos , Medicina de Precisión , Radiometría , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia Guiada por Imagen/instrumentación , Radioterapia de Intensidad ModuladaRESUMEN
Verification of dosimetric data computed by a treatment planning system is necessary in the commissioning process for any clinical software, just as it is necessary for any annual quality assurance testing. Direct verification of the dosimetric data is achievable when calculating the enhanced dynamic wedge (EDW) off-axis ratio at each point of interest. As mathematical models for hand-calculating such factors are still evolving, measurement of these external beam arrangements has proven significantly more accurate. This research presents a correlation for measured and planned data, specific for 6- and 18-MV photon beams on a Varian 21EX linear accelerator, using the EDW mode. Field generation was created using the Varian Eclipse treatment planning system. On treatment field delivery, the Sun Nuclear MapCHECK diode array was used to plot each beam profile in 2 dimensions. Wedge angles of 10 degrees , 15 degrees , 20 degrees , 25 degrees , 30 degrees , 45 degrees and 60 degrees were studied here, under isocentric geometry, at a fixed water equivalent depth of 15 cm. Field size dependence was considered with each wedge and energy combination, where symmetric apertures of 5 x 5 cm(2), 10 x 10 cm(2), 15 x 15 cm(2) and 20 x 20 cm(2) were used. Accurate dosimetric results were found to be achievable when using this treatment planning system to within 2.8% maximum deviation, and to within 1% deviation averaged over all. The diode array also proved to be simple and ideally suited for EDW measurements.
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Planificación de la Radioterapia Asistida por Computador , Algoritmos , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/instrumentaciónRESUMEN
UNLABELLED: Interactions between the life-sustaining ventricular assist devices and diagnostic therapies must be carefully considered to decrease the risk of inaccurate diagnostic imaging or pump failure. METHODS: The MVAD(®) pump, currently under investigational use, was tested for interaction with radiotracers in an in vitro flow-loop study. The radiotracers (18)F-sodium fluoride and (18)F-FDG were injected into a closed loop to determine the feasibility of direct imaging of the MVAD(®) pump in a PET scanner. RESULTS: No real-time changes were observed in pump operation, and there were no statistical differences in pump parameters (power consumption, speed, and estimated flow rate) between the baseline and circulation conditions. In addition, no effect was observed on any external components, including the permissive-action-link controller and the batteries powering the device. Imaging of the internal pump components was possible, with obscuration observed only in the portion of the pump where the spinning impeller is located. Retention of radiotracer in the pump components after circulation was minimal (<1%). CONCLUSION: PET imaging is an attractive diagnostic tool for patients with a ventricular assist device and may have additional utility outside its current use, detection of infection.
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Corazón Auxiliar , Miniaturización , Tomografía de Emisión de Positrones , Artefactos , Estudios de Factibilidad , Riesgo , Factores de TiempoAsunto(s)
Algoritmos , Protección Radiológica , Radioterapia de Intensidad Modulada/instrumentación , Braquiterapia/instrumentación , Braquiterapia/métodos , Humanos , Aceleradores de Partículas/instrumentación , Control de Calidad , Teleterapia por Radioisótopo/instrumentación , Teleterapia por Radioisótopo/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
Special care of superficial lesions surrounding critical structures, such as an eye, may require tight margins. When this is the case, small megavoltage electron treatment fields and nonstandard treatment distances become necessary. When the field size is found to be less than the practical range of the electron beam, dosimetric measurements should be performed. This research includes data proving that very small electron fields can be employed for treatment with appropriate beam flatness and penumbra. This is accomplished by first coming down the incident beam to a small field size, then secondly by adding a single lead sheet to the patient's skin surface. The aperture of the sheet is required to be greater than 2 x 2 cm2 in size, and must be cut properly to adequately confine the treatment area.
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Dosimetría por Película/métodos , Radioterapia Conformacional , Neoplasias Cutáneas/radioterapia , Humanos , Modelos Biológicos , Fantasmas de Imagen , Dosificación Radioterapéutica , Dosimetría TermoluminiscenteRESUMEN
An approach to dosimetry for total skin electron therapy (TSET) is discussed using the currently accepted TG-51 high-energy calibration protocol. The methodology incorporates water phantom data for absolute calibration and plastic phantom data for efficient reference dosimetry. The scheme is simplified to include the high-dose-rate mode conversion and provides support for its use, as it becomes more available on newer linear accelerators. Using a 6-field, modified Stanford technique, one may follow the process for accurate determination of absorbed dose.
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Algoritmos , Calibración/normas , Micosis Fungoide/radioterapia , Aceleradores de Partículas , Radioterapia de Alta Energía , Neoplasias Cutáneas/radioterapia , Irradiación Corporal Total , Humanos , RadiometríaRESUMEN
In a 2-part study, we first examined the results of 71 surveyed physicians who provided responses on how they address the management of patients who maintained either a pacemaker or a defibrillator during radiation treatment. Second, a case review study is presented involving 112 medical records reviewed at 18 institutions to determine whether there was a change in the radiation prescription for the treatment of the target cancer, the method of radiation delivery, or the method of radiation image acquisition. Statistics are provided to illustrate the level of administrative policy; the level of communication between radiation oncologists and heart specialists; American Joint Committee on Cancer (AJCC) staging and classification; National Comprehensive Cancer Network (NCCN) guidelines; tumor site; patient׳s sex; patient׳s age; device type; manufacturer; live monitoring; and the reported decisions for planning, delivery, and imaging. This survey revealed that 37% of patient treatments were considered for some sort of change in this regard, whereas 59% of patients were treated without regard to these alternatives when available. Only 3% of all patients were identified with an observable change in the functionality of the device or patient status in comparison with 96% of patients with normal behavior and operating devices. Documented changes in the patient׳s medical record included 1 device exhibiting failure at 0.3-Gy dose, 1 device exhibiting increased sensor rate during dose delivery, 1 patient having an irregular heartbeat leading to device reprogramming, and 1 patient complained of twinging in the chest wall that resulted in a respiratory arrest. Although policies and procedures should directly involve the qualified medical physicist for technical supervision, their sufficient involvement was typically not requested by most respondents. No treatment options were denied to any patient based on AJCC staging, classification, or NCCN practice standards.
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Desfibriladores Implantables/estadística & datos numéricos , Falla de Equipo/estadística & datos numéricos , Encuestas de Atención de la Salud , Neoplasias/radioterapia , Marcapaso Artificial/estadística & datos numéricos , Médicos/estadística & datos numéricos , Radioterapia/estadística & datos numéricos , Actitud del Personal de Salud , Estudios de Seguimiento , Humanos , Estados UnidosRESUMEN
Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes. Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.